RESUMO
Basaloid squamous cell carcinoma (BSCC), a variant of squamous cell carcinoma (SCC), is a rare and aggressive epithelial malignancy which has been reported in only 0.1-11 % of primary esophageal carcinomas. In this study, a comparison of clinicopathological features and protein expression between esophageal BSCC (EBSCC) and conventional esophageal SCC (ESCC) cases from Brazil was performed in order to find factors that can be relevant to better characterize EBSCC. The expression of HER2, epidermal growth factor receptor (EGFR), Ki-67, and cyclins (A, B1, and D1) in 111 cases (95 ESCC and 16 EBSCC) was evaluated by immunohistochemistry using tissue microarray. When the clinicopathological data were compared, no significant difference was found between the two histological types. Although the difference is not significant (p = 0.055), the EGFR expression was more frequent in the conventional ESCC than in the EBSCC group. Our results indicate that the clinicopathological profiles of conventional ESCC and EBSCC are similar and provide no indicators for differences in prognosis between these two groups.
Assuntos
Biomarcadores Tumorais , Carcinoma Basocelular/metabolismo , Carcinoma Basocelular/mortalidade , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidade , Idoso , Biópsia , Carcinoma Basocelular/patologia , Carcinoma Basocelular/terapia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Fatores de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: Vulvar carcinoma is an infrequent tumour, accounting for fewer than 3% of all malignant tumours that affect women, but its incidence is rising in the past few decades. In young women, the manifestation of the vulvar carcinoma is often linked to risk factors such as smoking and HPV infection, but most cases develop in women aged over 50 years through poorly understood genetic mechanisms. Rho-associated coiled-coil-containing protein kinase 1 (ROCK1) has been implicated in many cellular processes, but its function in vulvar cancer has never been examined. In this study, we aimed to determine the prognostic value of ROCK1 gene and protein analysis in vulvar squamous cell carcinoma (VSCC). METHODS: ROCK1 expression levels were measured in 16 vulvar tumour samples and adjacent normal tissue by qRT-PCR. Further, 96 VSCC samples were examined by immunohistochemistry (IHC) to confirm the involvement of ROCK1 in the disease. The molecular and pathological results were correlated with the clinical data of the patients. Sixteen fresh VSCC samples were analyzed by array-based comparative genomic hybridization (aCGH). RESULTS: In each pair of samples, ROCK1 levels were higher by qRT-PCR in normal tissue compared with the tumour samples (p = 0.016). By IHC, 100% of invasive front areas of the tumour and 95.8% of central tumour areas were positive for ROCK1. Greater expression of ROCK1 was associated with the absence of lymph node metastasis (p = 0.022) and a lower depth of invasion (p = 0.002). In addition, higher ROCK1 levels correlated with greater recurrence-free survival (p = 0.001). Loss of ROCK1 was independently linked to worse cancer-specific survival (p = 0.0054) by multivariate analysis. This finding was validated by IHC, which demonstrated enhanced protein expression in normal versus tumour tissue (p < 0.001). By aCGH, 42.9% of samples showed a gain in copy number of the ROCK1 gene. CONCLUSIONS: ROCK1 is lower expressed in tumour tissue when compared with adjacent normal vulvar epithelia. In an independent sample set of VSCCs, lower expression levels of ROCK1 correlated with worse survival rates and a poor prognosis. These findings provide important information for the clinical management of vulvar cancer.
Assuntos
Biomarcadores Tumorais , Neoplasias Vulvares/genética , Neoplasias Vulvares/mortalidade , Quinases Associadas a rho/genética , Adulto , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Hibridização Genômica Comparativa , Feminino , Expressão Gênica , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias Vulvares/patologia , Quinases Associadas a rho/metabolismoRESUMO
BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the sixth most frequent neoplasia in Brazil. It is usually associated with a poor prognosis because it is often at an advanced stage when diagnosed and there is a high frequency of lymph node metastases. It is important to know what prognostic factors can facilitate diagnosis, optimize therapeutic decisions, and improve the survival of these patients. A member of the epidermal growth factor receptor (EGFR) family, c-erbB-2, has received much attention because of its therapeutic implications; however, few studies involving fluorescence in situ hybridization (FISH) analysis of HER-2/neu gene amplification and protein expression in ESCC have been conducted. The aim of this study was to verify the presence of HER-2/neu gene amplification using FISH, and to correlate the results with immunohistochemical expression and clinical-pathological findings. METHODS: One hundred and ninety-nine ESCC cases were evaluated using the Tissue Microarray (TMA) technique. A polyclonal antibody against c-erbB-2 was used for immunohistochemistry. Analyses were based on the membrane staining pattern. The results were classified according to the Herceptest criteria (DAKO): negative (0/1+), potential positive (2+) and positive (3+). The FISH reactions were performed according to the FISH HER2 PharmDx (DAKO) protocol. In each case, 100 tumor nuclei were evaluated. Cases showing a gene/CEN17 fluorescence ratio > or = 2 were considered positive for gene amplification. RESULTS: The c-erbB-2 expression was negative in 117/185 cases (63.2%) and positive in 68 (36.8%), of which 56 (30.3%) were 2+ and 12 (6.5%) were 3+. No significant associations were found among protein expression, clinicopathological data and overall survival. Among the 47 cases analyzed, 38 (80.9%) showed no gene amplification while 9 (19.1%) showed amplification, as demonstrated by FISH. Cases that were negative (0/1+) and potential positive (2+) for c-erbB-2 expression by immunohistochemistry showed no gene amplification. However, all cases with gene amplification were positive (3+) by immunohistochemistry. According to univariate analysis, there was a significant difference (p = 0.003) in survival rates when cases with and without HER-2/neu amplification were compared. CONCLUSION: Our data demonstrate the correspondence between gene amplification and protein expression of HER-2/neu. Gene amplification is an indicator of poor prognosis in ESCC.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/mortalidade , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
Rodents constitute one of the most diversified mammalian orders. Due to the morphological similarity in many of the groups, their taxonomy is controversial. Karyotype information proved to be an important tool for distinguishing some species because some of them are species-specific. Additionally, rodents can be an excellent model for chromosome evolution studies since many rearrangements have been described in this group.This work brings a review of cytogenetic data of Brazilian rodents, with information about diploid and fundamental numbers, polymorphisms, and geographical distribution. We point out that, even with the recent efforts on cytogenetic studies in this group, many species lack karyotypic data. Moreover, we describe for the first time the karyotype of Carterodon sulcidens (Lund, 1838) (Family Echimyidae), a new fundamental number for an undescribed species of Neacomys Thomas, 1900 (Family Cricetidae, Subfamily Sigmodontinae), and illustrate the karyotype of a Brazilian specimen of Mus musculus Linnaeus, 1758 (Family Muridae). This review compiles the cytogenetic data on Brazilian rodents reported in the last three decades, after the last revision published in 1984, including synonyms, chromosomal variations, and geographic distribution. Additionally, it also reinforces that Brazilian biodiversity is still poorly known, considering the new data reported here.
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Objective: To describe the annual medical direct costs per hemophilia A (HA) patient in the Brazilian public healthcare system (SUS) and to understand and describe the patients' hospital journey, demographical characteristics, and the procedures in the. Methods: This retrospective analysis of DataSUS databases. Data from individuals with registries of HA treatment were gathered between January 1st, 2018, and June 30th, 2021. Besides the D66 ICD-10th code (HA), were also considered the occurrence of some procedures like factor VIII dosage and by-pass therapy dispensation or administration as inclusion criteria. Exclusion criteria were occurrence of factor IX dispensation and female patients were excluded, among others. A record linkage using sociodemographic characteristics was conducted to identify unique patients. Results: Were identified 2,298 individuals underwent ambulatory and 1,018 underwent hospital treatments. The results show that most patients are from the Southeast region of the country, white and middle-aged individuals. The median cost of HA treatment per patient-year was BRL 90.36 for ambulatory care and BRL 1,015.31 for hospital care procedures. The costs were significantly higher for more severe patients and for those between 12 and 18 years old (BRL 1,974.75 and BRL 1,049.09, respectively). Conclusion: The evidence demonstrated encourages the implementation of policies aiming to improve the quality of care provided to patients with HA. Providing referral centers for hemophiliac patients is primordial for the success of the treatment and can result in efficiency.
Objetivo: Descrever os custos médicos diretos anuais por paciente com hemofilia A (HA) no sistema público de saúde brasileiro (SUS) e compreender e descrever a jornada do paciente em âmbito hospitalar, as características demográficas e os procedimentos realizados no SUS. Métodos: Análise retrospectiva das bases de dados do DataSUS. Foram coletados dados de indivíduos com registro de tratamento de HA entre 1º de janeiro de 2018 e 30 de junho de 2021. Além do código D66 CID-10 (HA), foi considerada a ocorrência de procedimentos como dosagem do fator VIII e dispensação ou administração de terapia de by-pass como critérios de inclusão. Dentre os critérios de exclusão, destacam-se a dispensação do fator IX e indivíduos do sexo feminino. Um pareamento de registros usando características sociodemográficas foi realizado para identificar pacientes únicos. Resultados: Foram identificados 2.298 indivíduos em tratamento ambulatorial e 1.018 em tratamento hospitalar. Os resultados mostraram que a maioria dos pacientes são da região Sudeste do país, brancos e de meia-idade. O custo médio do tratamento da HA por paciente-ano foi de R$ 90,36 para atendimento ambulatorial e de R$ 1.015,31 para atendimento hospitalar. Os custos foram significativamente maiores para pacientes mais graves e entre 12 e 18 anos (R$ 1.974,75 e R$ 1.049,09, respectivamente). Conclusão: As evidências demonstradas incentivam a implementação de políticas que visem melhorar a qualidade da assistência prestada aos pacientes com HA. A disponibilização de centros de referência para pacientes hemofílicos é primordial para o sucesso do tratamento e pode resultar em maior eficiência.
Assuntos
Epidemiologia , Efeitos Psicossociais da Doença , Hemofilia ARESUMO
Objective: Understanding unmet needs related to hemophilia A management in Brazil is critical for supporting decision-making. Methods: A modified Delphi consensus panel was conducted. Hematologists with extensive experience treating hemophilia in the Brazilian Public Health System were invited to answer questions regarding indicators of severe hemophilia prophylaxis effectiveness, emicizumab treatment indications, and bypassing agents used to reduce bleeding in patients with inhibitors, immune tolerance induction (ITI) use, and adherence. The consensus was defined as ≥75% of votes in Round 1 or using a 5-point Likert-type scale (1 = strongly disagree, 2 = disagree, 3 = neither agree nor disagree, 4 = agree, and 5 = strongly agree) in Round 2, which included questions not reaching minimum cut-off in the first step. Results: Nine expert panelists with extensive experience in the Brazilian Public Health System participated. The panel reached an agreement on recommendations about prophylaxis, bleeding treatment patterns, and bleeding sites. From patients' perspectives, venous access and infusion frequency were the most significant barriers to improving patient treatment. According to most experts, emicizumab will not replace ITI or long-term factor VIII therapy. Still, emicizumab was thought to be a good therapeutic option for patients with difficult venous access, patients requiring central venous access, in the presence of inhibitors, or patients experiencing infusion-related pain. Conclusion: The information gleaned from this study may be helpful to both decision-makers and those in charge of developing healthcare economic models for the treatment of hemophilia A in Brazil.
Objetivo: É fundamental entender as necessidades não atendidas relacionadas ao manejo da hemofilia A no Brasil. Métodos: Foi conduzido um painel Delphi modificado. Foram convidados hematologistas com vasta experiência no tratamento de hemofilia no SUS para responder a perguntas sobre indicadores de eficácia da profilaxia, indicações de tratamento com emicizumabe, uso de agentes de bypass, uso de indução de tolerância imunológica (ITI) e adesão. O consenso foi definido como ≥75% dos votos na rodada 1 ou usando uma escala do tipo Likert de 5 pontos (1 = discordo totalmente, 2 = discordo, 3 = não concordo nem discordo, 4 = concordo e 5 = concordo totalmente) na segunda rodada, que incluiu questões que não atingiram o corte mínimo na primeira etapa. Resultados: Nove especialistas participaram e houve consenso sobre recomendações para profilaxia, padrões de tratamento de sangramento e locais de sangramento. O acesso venoso e a frequência da infusão foram identificados como as barreiras mais significativas para melhorar o tratamento do paciente. De acordo com a maioria, emicizumabe não substituirá a ITI ou tratamento com fator VIII de longo prazo. Emicizumabe foi considerado uma boa opção terapêutica para
Assuntos
Terapêutica , Hemofilia B , Prevenção de DoençasRESUMO
UNLABELLED: Vulvar squamous cell carcinoma (VSCC) is a rare disease that has a high mortality rate (â¼40%). However, little is known about its molecular signature. Therefore, an integrated genomics approach, based on comparative genome hybridization (aCGH) and genome-wide expression (GWE) array, was performed to identify driver genes in VSCC. To achieve that, DNA and RNA were extracted from frozen VSCC clinical specimens and examined by aCGH and GWE array, respectively. On the basis of the integration of data using the CONEXIC algorithm, PLXDC2 and GNB3 were validated by RT-qPCR. The expression of these genes was then analyzed by IHC in a large set of formalin-fixed paraffin-embedded specimens. These analyses identified 47 putative drivers, 46 of which were characterized by copy number gains that were concomitant with overexpression and one with a copy number loss and downregulation. Two of these genes, PLXDC2 and GNB3, were selected for further validation: PLXDC2 was downregulated and GNB3 was overexpressed compared with non-neoplastic tissue. By IHC, both proteins were ubiquitously expressed throughout vulvar tissue. High expression of GNB3 and low PLXDC2 immunostaining in the same sample was significantly associated with less lymph node metastasis and greater disease-free survival. On the basis of a robust methodology never used before for VSCC evaluation, two novel prognostic markers in vulvar cancer are identified: one with favorable prognosis (GNB3) and the other with unfavorable prognosis (PLXDC2). IMPLICATIONS: This genomics study reveals markers that associate with prognosis and may provide guidance for better treatment in vulvar cancer. Mol Cancer Res; 14(8); 720-9. ©2016 AACR.
Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias Vulvares/genética , Intervalo Livre de Doença , Feminino , Humanos , Resultado do Tratamento , Neoplasias Vulvares/patologiaRESUMO
The role of the extracellular non-coding RNAs, particularly microRNAs present in tumor-derived extravesicles, has been intensively exploited in human cancer as a promising tool for diagnostic and prognostic purposes. Current knowledge on exosomes shows an important role not only as vehicles in the intercellular communication, but the transfer of their content can specifically modulate the surrounding microenvironment, leading to tumor development and progression and affecting therapy response. Based on this, much effort has focused on understanding the mechanisms behind the biology of exosomes and their closely interaction with non-coding RNAs as an efficient tool in tumor diagnostic and therapy. Here we summarize the current knowledge on extracellular and exosomes-enclosed non-coding RNAs, and their importance as potential biomarkers and mediators of intercellular communication in tumor biology.
Assuntos
Exossomos/fisiologia , Técnicas de Diagnóstico Molecular , Neoplasias/diagnóstico , Neoplasias/terapia , RNA não Traduzido/fisiologia , Animais , Exossomos/patologia , Humanos , MicroRNAs/fisiologia , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Diagnóstico Molecular/tendências , Neoplasias/genética , Neoplasias/patologia , RNA não Traduzido/uso terapêuticoRESUMO
Rodents constitute one of the most diversified mammalian orders. Due to the morphological similarity in many of the groups, their taxonomy is controversial. Karyotype information proved to be an important tool for distinguishing some species because some of them are species-specific. Additionally, rodents can be an excellent model for chromosome evolution studies since many rearrangements have been described in this group. This work brings a review of cytogenetic data of Brazilian rodents, with information about diploid and fundamental numbers, polymorphisms, and geographical distribution. We point out that, even with the recent efforts on cytogenetic studies in this group, many species lack karyotypic data. Moreover, we describe for the first time the karyotype of Carterodon sulcidens (Lund, 1838) (Family Echimyidae), a new fundamental number for an undescribed species of Neacomys Thomas, 1900 (Family Cricetidae, Subfamily Sigmodontinae), and illustrate the karyotype of a Brazilian specimen of Mus musculus Linnaeus, 1758 (Family Muridae). This review compiles the cytogenetic data on Brazilian rodents reported in the last three decades, after the last revision published in 1984, including synonyms, chromosomal variations, and geographic distribution. Additionally, it also reinforces that Brazilian biodiversity is still poorly known, considering the new data reported here.